A few people in the stem cell field keep arguing that adult pluripotent stem cells exist, including so-called “very small embryonic-like stem cells” or VSEL stem cells.
These days the supposed cells are called VSELs or V-cells too.
Only a handful of researchers have ever been able to report finding and studying these cells. Others including very respected labs have tried and reported no luck.
Some stem cell researchers believe that VSELs are thoroughly debunked. So what write about them now? I’ve been getting an increasing number of questions from patients about clinics selling these alleged cells or similar ones. The clinics claim to treat numerous conditions. There have also been some other recent developments lending more skepticism to the VSELs existence.
Today’s post is an overview and update.
What’s in this article
What are VSEL stem cells? | VSELs probably aren’t real | VSEL isolation methods | VSEL treatment? Looking Ahead | References
What are VSELs?
As their name suggests, these cells are supposed to be (1) very small and (2) have significant similarities to embryonic stem cells. VSEL stem cells are claimed to be adult pluripotent stem cells, which seems counterintuitive.
While it is formally possible that adult human or mouse tissues have pluripotent stem cells, to me as a stem cell biologist it seems extremely unlikely.
One reason I’m so skeptical is that if these cells really existed, we should see more adults getting an usual kind of tumor called teratomas. Pluripotent stem cells have the ability to grow into these odd tumors. Some VSEL supporters claim the pluripotency but say the cells generally don’t make teratoma. How is that possible? Why don’t mice or humans, the two main organisms from which VSELs supposed have been isolated, get teratomas all the time?
Other researchers claim that another similar kind of adult pluripotent stem cell cell type called MUSE cells exist. MUSE cells are also supposed to be powerful adult stem cells.
As with the VSEL arena, somehow MUSE cells can only be found and studied by a few labs.
VSEL stem cells probably aren’t real
When only very few labs can readily identify rare cells it raises further skepticism.
For me, the turning point on VSELs was a few years back when they received a trio of bad news. Three skeptical and even outright negative pieces came out:
- A research article in Stem Cell Reports from Irv Weissman’s group (Miyanishi, et al.) entitled “Do Pluripotent Stem Cells Exist in Adult Mice as Very Small Embryonic Stem Cells?”
- An opinion piece in Cell Stem Cell by Henry Nicholls
- A skeptical newsy piece in Nature by Alison Abbott entitled, “Doubt cast over tiny stem cells”.
A quote from the Abbott piece citing the Weissman article tells just how much skepticism there is:
“…in a major blow to the field, a paper published on 24 July in Stem Cell Reports suggests that the diminutive stem cells are not real1.”
Dr. Mariusz Ratajczak (see image at left from Nature) may be the main proponent of VSELs. He has published a huge number of papers reporting on these cells.
Other VSEL supporters are still out there too.
However, most stem cell biologists do not believe in VSELs.
In a Cell Stem Cell piece, entitled “VSELs: Is Ideology Overtaking Science”, Henry Nicholls discusses the main VSEL issues and includes a quote from stem cell leader, George Daley, which is very critical of VSELs:
“This rigorous approach just hasn’t been taken with VSELs. I find the work mystifying and lacking in rigor.”
That is very harsh for a public statement.
Note that Dr. Elisabeth Bik recently reported identifying more than two dozen VSEL papers with concerning issues. For instance, Bik found that many figures seem to have puzzling features. See an example above.
All in the isolation methods?
In the past, Ratajczak explained the difficulties that other researchers have had with VSELs as being due to lack of consistency in experimental methodology:
“In studying rare populations of cells, one needs to compare apples to apples, which unfortunately was not done”
From another VSEL stem cell researcher:
“I don’t see the controversy — we have seen bone grow” from VSELs in mice, says Russell Taichman, a researcher in dental medicine at the University of Michigan in Ann Arbor. Taichman will be running the Neostem-backed VSEL trial, which will look for bone regrowth in dental patients. Announced in April, the trial is awaiting approval by the US Food and Drug Administration.
I reached out to Taichman by email to ask about this current thinking on VSELs last week, but got no reply. If I hear back I’ll include an update.
Abbott’s piece suggests there has been a political element to the VSEL controversy too involving alleged retaliation against those who report negative findings about VSEL:
“… Józef Dulak at the Jagiellonian University in Krakow, failed to find traces of VSELs in his experiments. When he published his findings in May, Ratajczak tried to force him out of the consortium. Dulak, like Weissman, found no molecular signatures associated with pluripotency in any mouse bone-marrow cells smaller than 7 micrometres across.”
There are 7 trial listings on Clinicaltrials.gov for a search for VSELs. Five of these seem to be specific to VSEL research and none are active.
Let’s say there are no VSELs normally in adult tissues. In that context, could some altered VSEL-like cells pop up due to the stress of the isolation process? I really doubt it.
VSEL treatment? Looking ahead
In the end, science should guide us here.
The best data so far suggest that VSELs are probably not real. Yet at the same time as I said more patients are contacting me. They have run across marketing for supposed VSEL therapies. The patients ask about clinics that are selling VSEL treatments or MUSE cells to treat numerous conditions. It’s concerning because if, as seems almost certain, VSELs are not real, then what are the clinics injecting into people? What are the risks?
It was surprisingly easy to find clinics selling VSELs on the web. Some are even in the U.S. It seems likely that the FDA would view VSELs as biological drugs. There are no FDA-approved VSEL treatments.
With the tin mind, why are so many of these unproven clinics starting to sell VSEL “therapies” then?
It seems that it boils down to trying to make profits in new ways off of vulnerable patients.
References
- Bik piece on troubled VSEL papers
- A research article in Stem Cell Reports from Irv Weissman’s group
- An opinion piece in Cell Stem Cell by Henry Nicholls
- A skeptical newsy piece in Nature by Alison Abbott entitled, “Doubt cast over tiny stem cells”.
- VSEL clinical trial listings.
- Dulak lab paper, Murine bone marrow Lin⁻Sca⁻1⁺CD45⁻ very small embryonic-like (VSEL) cells are heterogeneous population lacking Oct-4A expression.
Hi Dr Knoepfler – I was hoping your conclusions would lean toward the positive. It’s frustrating when the hype overwhelms the reality.
A business partner of mine recently paid for extensive VSELS treatment. He’s bullish on the results. But it also looked very similar to classic cosmetic treatments (like an acid or abrasive peel), followed by red light therapy.
I’m hoping progress continues to be made in this research. It’s time we realized some significant breakthroughs.
Thanks for providing some solid insights. It’s much appreciated.
Hey Mark, are you able to report back the results from your friends experience with VSEL? It would certainly be relevant info at this point.
What about Vsel cells taken from a persons own bone marrow?
What’s the difference between these and the other stem cell therapies that don’t work?
Thanks for the update. I am very disappointed to hear that clinics are promoting “VESL” therapies, which is surely nonsense. These clinics just take money from patients and deny them opportunities for therapies or clinical trials that may provide some benefit.
Perhaps Dr. Ratajczak who has done the most to promote VESL research should ask these clinics to stop VESL therapies that are not done as part of a well run clinical trial that could actually help define if there is a benefit or not. Indeed, if he thinks VESLs are helpful, that is the only way this would actually be shown.
Dan,
That’s an interesting suggestion for Dr. R.
I’m also hearing from patients asking about MUSE cell “treatments” from clinics. In the case of MUSE cells there are quite a few clinical trials going in Japan and active funding last time I checked.